Uveal melanoma is the most common malignant intraocular cancer among adults
with an incidence of 5.1 cases per 100.000 inhabitants. The case fatality rate
is accounted for by the high risk of metastasis. The most affected organs are
the liver, followed by lung, bone and skin. The diagnosis is often found in a
routine examination because of the long asymptomatically development of this
cancer. To diagnose this disease different techniques can be used, which until
have not reduced the mortality rate. As with all kinds of neoplasia,
dysfunctions of cellular homoestasis may lead to a progression of the cancer.
An important second messenger is calcium because it is involved in many
signalling pathways within the cell. The family of calcium-regulated channels
involves transient receptor potential channels (TRPs), which are often
dysregulated in neoplasia. In this study, we compared the malignant uveal
melanoma cell line 92.1 with healthy uveal melanocytes from pigs for
functional expression of the TRP subtypes TRPV1 (vanilloid receptor, capsaicin
receptor) and TRPM8 (melastatin receptor, menthol receptor). For the
investigations, we used high sensitive functional assays like calcium imaging
and planar patch-clamping. In healthy uveal melanocytes capsaicin, a TRPV1
agonist, induced increases of intracellular calcium and whole-cell currents
whereas the TRPM8 agonist icilin did not clearly induce calcium regulation in
these cells. In contrast such calcium increase could be stimulated by both,
capsaicin and icilin in malignant uveal melanoma cells. The changes in ion
current behaviour indicate functional TRPM8 and TRPV1 expression since their
activation could be blocked with either capsazepine (CPZ, TRPV1blocker) or
BCTC (TRPM8 blocker). The identification of significant differences in the
functional expression of both channels opens new treatment options. Nether the
less these new findings can not be easily transferred to a living organism. On
the one side, we used uveal cells out of a pig eye. On the other hand, it is
problematic to compare in vitro data with a complex human being. There is a
need for much more research before a clinical benefit can be achieved.